2024
Iguratimod, an allosteric inhibitor of macrophage migration inhibitory factor (MIF), prevents mortality and oxidative stress in a murine model of acetaminophen overdose
Bloom J, Pantouris G, He M, Aljabari B, Mishra L, Manjula R, Parkins A, Lolis E, Al-Abed Y. Iguratimod, an allosteric inhibitor of macrophage migration inhibitory factor (MIF), prevents mortality and oxidative stress in a murine model of acetaminophen overdose. Molecular Medicine 2024, 30: 43. PMID: 38539088, PMCID: PMC10976746, DOI: 10.1186/s10020-024-00803-0.Peer-Reviewed Original ResearchConceptsMode of inhibitionAllosteric inhibitorsActive site pocketMigration inhibitory factorSite pocketInhibitory factorProtein crystallographyTautomerase active siteOxidative stressT-614Murine modelDrug modePleiotropic cytokineNon-competitive type of inhibitionAPAP overdoseActive siteMacrophage migration inhibitory factorInhibition constantType of inhibitionInhibitor of macrophage migration inhibitory factorKinetic analysisBackgroundMacrophage migration inhibitory factorAcetaminophen overdoseIn vivo experimentsMultiple small molecule inhibitors
2023
Plant MDL proteins synergize with the cytokine MIF at CXCR2 and CXCR4 receptors in human cells
Spiller L, Manjula R, Leissing F, Basquin J, Bourilhon P, Sinitski D, Brandhofer M, Levecque S, Gerra S, Sabelleck B, Zhang L, Feederle R, Flatley A, Hoffmann A, Panstruga R, Bernhagen J, Lolis E. Plant MDL proteins synergize with the cytokine MIF at CXCR2 and CXCR4 receptors in human cells. Science Signaling 2023, 16: eadg2621. PMID: 37988455, DOI: 10.1126/scisignal.adg2621.Peer-Reviewed Original ResearchConceptsMammalian macrophage migration inhibitory factorHetero-oligomeric complexesHigh structural similarityMultifunctional inflammatory cytokineHuman lung epithelial cellsYeast reporter systemReporter systemLung epithelial cellsPlant leavesFunctional similarityCellular responsesHuman cellsPharmacological inhibitorsDopachrome tautomeraseFunctional implicationsX-ray crystallographyMacrophage migration inhibitory factorStructural similarityEpithelial cellsMigration inhibitory factorCXCR4 receptorProteinTautomerase activityCellsMIF receptor
2016
Macrophage Migration Inhibitory Factor-CXCR4 Receptor Interactions*
Rajasekaran D, Gröning S, Schmitz C, Zierow S, Drucker N, Bakou M, Kohl K, Mertens A, Lue H, Weber C, Xiao A, Luker G, Kapurniotu A, Lolis E, Bernhagen J. Macrophage Migration Inhibitory Factor-CXCR4 Receptor Interactions*. Journal Of Biological Chemistry 2016, 291: 15881-15895. PMID: 27226569, PMCID: PMC4957068, DOI: 10.1074/jbc.m116.717751.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorChemokine receptorsCXCR4 receptorRole of MIFMIF's biological activityMigration inhibitory factorChemokine receptor interactionsFunctional CXCR4 receptorsClassical chemokine receptorsChemokine-like activityPartial allosteric agonistRegions of CXCR4Inflammatory cytokinesReceptor CD74Leukocyte recruitmentAllosteric agonistInhibitory factorCXCR4Non-cognate interactionsReceptorsPharmacological reagentsReceptor interactionArray analysisGenetic strainsCritical biological responses
2001
Glucocorticoid counter regulation: macrophage migration inhibitory factor as a target for drug discovery
Lolis E. Glucocorticoid counter regulation: macrophage migration inhibitory factor as a target for drug discovery. Current Opinion In Pharmacology 2001, 1: 662-668. PMID: 11757824, DOI: 10.1016/s1471-4892(01)00112-6.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid SequenceAnimalsCOP9 Signalosome ComplexDNA-Binding ProteinsDrug DesignGenes, p53GlucocorticoidsHumansInflammationInflammation MediatorsIntracellular Signaling Peptides and ProteinsMacrophage Migration-Inhibitory FactorsMembrane ProteinsMolecular Sequence DataNeoplasmsNeovascularization, PathologicPeptide HydrolasesPhosphoproteinsStructure-Activity RelationshipTranscription FactorsConceptsMacrophage migration inhibitory factorMigration inhibitory factorContribution of MIFInhibitory factorElevated MIF levelsMIF's biological activityActivity of CD4Natural killer cellsInflammatory neurological diseasesInflammatory lung diseasesMIF levelsUlcerative colitisKiller cellsRheumatoid arthritisLung diseaseInflammatory diseasesT cellsHuman studiesNeurological diseasesTherapeutic interventionsDiseaseEndothelial cellsNumber of diseasesIntracellular regulatory proteinsCancerDevelopment of chronic colitis is dependent on the cytokine MIF
de Jong Y, Abadia-Molina A, Satoskar A, Clarke K, Rietdijk S, Faubion W, Mizoguchi E, Metz C, Sahli M, ten Hove T, Keates A, Lubetsky J, Farrell R, Michetti P, van Deventer S, Lolis E, David J, Bhan A, Terhorst C. Development of chronic colitis is dependent on the cytokine MIF. Nature Immunology 2001, 2: 1061-1066. PMID: 11668338, DOI: 10.1038/ni720.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAutoimmune DiseasesBone Marrow TransplantationChronic DiseaseColitisCrohn DiseaseDNA-Binding ProteinsFemaleHumansImmunization, PassiveLipopolysaccharidesMacrophage ActivationMacrophage Migration-Inhibitory FactorsMaleMiceMice, KnockoutModels, AnimalNuclear ProteinsRadiation ChimeraWeight LossConceptsMacrophage migration inhibitory factorCytokine macrophage migration inhibitory factorMIF-deficient miceCrohn's diseaseRole of MIFImmune systemPlasma MIF concentrationMucosal immune systemInnate immune cellsInnate immune systemChronic colitisMIF concentrationsExperimental colitisMIF productionMurine colitisImmune cellsColitisIntestinal bacteriaInhibitory factorDiseaseNew targetsMiceLipopolysaccharideCell typesPatientsCCR2 and CCR5 receptor‐binding properties of herpesvirus‐8 vMIP‐II based on sequence analysis and its solution structure
Shao W, Fernandez E, Sachpatzidis A, Wilken J, Thompson D, Schweitzer B, Lolis E. CCR2 and CCR5 receptor‐binding properties of herpesvirus‐8 vMIP‐II based on sequence analysis and its solution structure. The FEBS Journal 2001, 268: 2948-2959. PMID: 11358512, DOI: 10.1046/j.1432-1327.2001.02184.x.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBinding SitesChemokinesChemokines, CCDimerizationEpitopesMagnetic Resonance SpectroscopyModels, ChemicalModels, MolecularMolecular Sequence DataPeptide BiosynthesisProtein BindingProtein ConformationProtein FoldingProtein Structure, SecondaryReceptors, CCR2Receptors, CCR5Receptors, ChemokineSequence Analysis, ProteinSequence Homology, Amino AcidConceptsHuman herpesvirus 8VMIP-IIChemokine receptorsCC chemokinesReceptor-binding propertiesNumerous chemokine receptorsPresence of epitopesHIV-1 viral entryHuman CC chemokineReceptor CCR2Kaposi's sarcomaHerpesvirus 8Infectious agentsCCR2Viral entryReceptor bindingReceptor specificityCCR5ChemokinesSarcomaReceptorsReceptor subfamiliesMagnetic resonanceBroad receptor specificityProtein II
2000
Expression and coreceptor activity of STRL33/Bonzo on primary peripheral blood lymphocytes.
Sharron M, Pöhlmann S, Price K, Lolis E, Tsang M, Kirchhoff F, Doms R, Lee B. Expression and coreceptor activity of STRL33/Bonzo on primary peripheral blood lymphocytes. Blood 2000, 96: 41-9. PMID: 10891428, DOI: 10.1182/blood.v96.1.41.013k53_41_49.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDB-LymphocytesCell LineCells, CulturedFlow CytometryGenes, ReporterGenetic VectorsGreen Fluorescent ProteinsHumansKiller Cells, NaturalLuminescent ProteinsMacaca mulattaReceptors, CCR5Receptors, ChemokineReceptors, CXCR6Receptors, CytokineReceptors, G-Protein-CoupledReceptors, VirusTransfectionConceptsPeripheral blood lymphocytesPeripheral blood mononuclear cellsSimian immunodeficiency virusCoreceptor activityRelevant coreceptorAlternative coreceptorsBlood lymphocytesHuman immunodeficiency virus-1 (HIV-1) infectionMost simian immunodeficiency virusesPrimary peripheral blood lymphocytesHuman peripheral blood lymphocytesTumor-infiltrating lymphocytesNatural killer cellsBlood mononuclear cellsVirus-1 infectionPotent CXCR4 antagonistSIV Env proteinsMacaque systemKiller cellsImmunodeficiency virusMononuclear cellsMajor coreceptorMaternal isolatesSIV envelopeSTRL33
1999
Pro-1 of Macrophage Migration Inhibitory Factor Functions as a Catalytic Base in the Phenylpyruvate Tautomerase Activity † , ‡
Lubetsky J, Swope M, Dealwis C, Blake P, Lolis E. Pro-1 of Macrophage Migration Inhibitory Factor Functions as a Catalytic Base in the Phenylpyruvate Tautomerase Activity † , ‡. Biochemistry 1999, 38: 7346-7354. PMID: 10353846, DOI: 10.1021/bi990306m.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionAnimalsBinding SitesCatalysisCrystallography, X-RayEnzyme ActivationGlycineHumansHydrogen-Ion ConcentrationIntramolecular OxidoreductasesMacromolecular SubstancesMacrophage Migration-Inhibitory FactorsMethionineMutagenesis, Site-DirectedNuclear Magnetic Resonance, BiomolecularPhenylpyruvic AcidsProlineRecombinant ProteinsConceptsMacrophage migration inhibitory factorMacrophage migration inhibitory factor (MIF) functionsAnti-inflammatory effectsMigration inhibitory factorImportant immunoregulatory moleculeTautomerase activityImmunoregulatory moleculesPhenylpyruvate tautomerase activityInhibitory factorP-hydroxyphenylpyruvateGlucocorticoidsPro-1CytokinesActivityMacrophage migration inhibitory factor: Cytokine, hormone, or enzyme?
Swope M, Lolis E. Macrophage migration inhibitory factor: Cytokine, hormone, or enzyme? 1999, 139: 1-32. PMID: 10453691, DOI: 10.1007/bfb0033647.Peer-Reviewed Original Research
1998
Direct link between cytokine activity and a catalytic site for macrophage migration inhibitory factor
Swope M, Sun H, Blake P, Lolis E. Direct link between cytokine activity and a catalytic site for macrophage migration inhibitory factor. The EMBO Journal 1998, 17: 3534-3541. PMID: 9649424, PMCID: PMC1170690, DOI: 10.1093/emboj/17.13.3534.Peer-Reviewed Original ResearchConceptsN-terminal prolineN-terminal regionStructure-based inhibitorsMultiple sequence alignmentThree-dimensional structureInvariant residuesEntire polypeptideMicrobial enzymesCatalytic basePro-1Sequence alignmentMIF homologuesCytokine activityHuman macrophage migration inhibitory factorCatalytic siteProlineInhibitory factorHomologuesUnderlying biological activityP-hydroxyphenylpyruvateProteinMacrophage migration inhibitory factorActive siteBiological activitySolution Structure of Murine Macrophage Inflammatory Protein-2 † , ‡
Shao W, Jerva L, West J, Lolis E, Schweitzer B. Solution Structure of Murine Macrophage Inflammatory Protein-2 † , ‡. Biochemistry 1998, 37: 8303-8313. PMID: 9622482, DOI: 10.1021/bi980112r.Peer-Reviewed Original Research
1997
Functional and receptor binding characterization of recombinant murine macrophage inflammatory protein 2: Sequence analysis and mutagenesis identify receptor binding epitopes
Jerva L, Lolis E, Sullivan G. Functional and receptor binding characterization of recombinant murine macrophage inflammatory protein 2: Sequence analysis and mutagenesis identify receptor binding epitopes. Protein Science 1997, 6: 1643-1652. PMID: 9260277, PMCID: PMC2143775, DOI: 10.1002/pro.5560060805.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntigens, CDBase SequenceCell LineChemokine CXCL2Chemokines, CXCCloning, MolecularDNA PrimersEpitopesHumansIntercellular Signaling Peptides and ProteinsMiceMolecular Sequence DataMonokinesMutagenesis, Site-DirectedNeutrophilsReceptors, InterleukinReceptors, Interleukin-8ARecombinant ProteinsSequence Homology, Amino Acid
1995
Salvaging recombinants from low-efficiency ligase reactions for more efficient subcloning.
Sun H, Lolis E. Salvaging recombinants from low-efficiency ligase reactions for more efficient subcloning. BioTechniques 1995, 18: 644-6, 648, 650. PMID: 7598899.Peer-Reviewed Original Research
1992
Preliminary crystallographic analysis of murine macrophage inflammatory protein 2
Lolis E, Sweet R, Cousens L, Tekamp-Olson P, Sherry B, Cerami A. Preliminary crystallographic analysis of murine macrophage inflammatory protein 2. Journal Of Molecular Biology 1992, 225: 913-915. PMID: 1602491, DOI: 10.1016/0022-2836(92)90411-c.Peer-Reviewed Original Research